The Use of Erythropoietin to Reprogram Oral and Craniofacial Stem Cells

使用促红细胞生成素重新编程口腔和颅面干细胞

• 批准号: 7936104
• 负责人: DAVID H. KOHN
• 金额: $ 48.55万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-22 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7936104
• 关键词: Achievement; Acute; Address; Adenoviruses; Adult; Affect; Animals; Apoptosis; Area; Beds; Biology; Biomedical Engineering; Blood; Bone Development; Bone Marrow; Bone Regeneration; Cancer Patient; Cell Culture Techniques; Cell Separation; Cell Therapy; Cell Transplants; Cell surface; Cells; Cephalic; Chronic; Cicatrix; Clinical; Coupling; Data; Defect; Disease; Elements; Erythropoietin; Exclusion; Face; Fibrosis; Fracture Healing; Healed; Hematopoiesis; Hematopoietic System; Hematopoietic stem cells; Hemorrhage; Human; In Vitro; Inflammation; Marrow; Mesenchymal; Mesenchymal Stem Cells; Modality; Modeling; Molecular; Natural regeneration; Occupations; Operative Surgical Procedures; Oral; Oral cavity; Osteogenesis; Pathway interactions; Phenotype; Physiological; Positioning Attribute; Process; Production; Radiation Toxicity; Radiation therapy; Reconstructive Surgical Procedures; Research Personnel; Science; Somatic Cell; Stem cells; Stromal Cells; Therapeutic; Tissues; Transplantation; Trauma; Vascular blood supply; Wound Healing; base; bone morphogenetic protein 2; bone morphogenetic protein 6; cell type; craniofacial; craniofacial complex; gene therapy; healing; human tissue; improved; in vivo; novel strategies; oral tissue; osteoblast differentiation; prospective; receptor; regenerative; regenerative therapy; repaired; scaffold; skeletal; stem cell population; tissue regeneration; translational study; vector; wound

DESCRIPTION (provided by applicant): The Use of Erythropoietin to Reprogram Oral and Craniofacial Stem Cells. This project directly addresses Challenge Area (14)-Stem Cells, specifically 14-DE-101* Reprogramming of Cells from Oral and Craniofacial Tissues in which we developed a novel approach for partial reprogramming of somatic stem cells of the oral and craniofacial complex using erythropoietin (Epo) for cell- based therapies to heal and restore these tissues following disease or trauma. We have identified that Epo is able to induce bone formation in vitro as well as in vivo. We have also purified mesenchymal stem cell (MSC) population that maintains its multi-lineage potential both in vivo and in vitro. Most importantly, we can isolate MSCs using cell surface markers that allows us to prospectively isolate the cells without culture. This sets us apart from others in the mesenchymal biology field. In this project we will combined our two studies to determine if Epo can partially reprogram adult MSCs to be used for regeneration of non-healing wounds This proposal will serve as a critical shift in our paradigm and a spring board for application of bioengineering to controlling tissue regeneration that we believe will ultimately be used in a broad range of human tissues. Our overall hypothesis is that erythropoietin (Epo) can be used to reprogram skeletal precursors and mesenchymal stem cells that can be harnessed for skeletal repair. Our approach will be to determine if Epo can be used to reprogram bone marrow stromal cells, and later MSCs, to facilitate osseous repair in nonhealing and irradiated critical sized boney defects. Aim 1. To determine the extent to which BMSCs reprogrammed to express EPO are capable of regenerating critical sized cranio-facial defects compromised by radiation therapy. Aim 2: To determine whether Epo can partially reprogram MSCs for cell-based therapies to heal and restore tissues following disease or trauma. This project will promote job creation, and accelerate the pace and achievement of science. The completion of the project is feasible in a two year timeframe and our group will then be in an outstanding position to propose and complete more mechanistic and translational studies in oral and craniofacial regeneration. 2 Erythropoietin can be used to reprogram skeletal precursors and mesenchymal stem cells that can be harnessed for skeletal repair.

描述（由申请人提供）：使用促红细胞生成素重新编程口腔和颅面干细胞。该项目直接解决挑战领域（14）-干细胞，特别是14-DE-101* 口腔和颅面组织细胞的重编程，其中我们开发了一种使用促红细胞生成素（Epo）对口腔和颅面复合体的体干细胞进行部分重编程的新方法，用于基于细胞的治疗，以治愈和恢复疾病或创伤后的这些组织。我们已经确定Epo能够在体外和体内诱导骨形成。我们还纯化了间充质干细胞（MSC）群体，在体内和体外都保持其多谱系潜力。最重要的是，我们可以使用细胞表面标记物分离MSC，这使得我们能够在不进行培养的情况下前瞻性地分离细胞。这使我们在间充质生物学领域与众不同。在这个项目中，我们将结合我们的两项研究，以确定Epo是否可以部分重编程成人MSC用于非愈合伤口的再生。这个建议将成为我们范式的关键转变，也是生物工程应用于控制组织再生的跳板，我们相信最终将用于广泛的人体组织。我们的总体假设是，促红细胞生成素（Epo）可用于重新编程骨骼前体细胞和间充质干细胞，可用于骨骼修复。我们的方法是确定促红细胞生成素是否可用于重编程骨髓基质细胞，以及随后的间充质干细胞，以促进不愈合和辐射临界尺寸骨缺损的骨修复。目标1.确定BMSC重编程表达EPO的能力在多大程度上能够再生放射治疗损害的临界尺寸的颅面缺损。目的2：确定Epo是否可以部分重编程MSC用于基于细胞的治疗，以愈合和恢复疾病或创伤后的组织。该项目将促进创造就业机会，加快科学的步伐和成就。该项目的完成是可行的，在两年的时间内，我们的小组将在一个突出的位置，提出和完成更多的口腔和颅面再生的机制和转化研究。2促红细胞生成素可用于重新编程骨骼前体和间充质干细胞，这些细胞可用于骨骼修复。